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Its unusual independence of extracellular K\n                      <jats:sup>+<\/jats:sup>\n                      ([K\n                      <jats:sup>+<\/jats:sup>\n                      ]\n                      <jats:sub>o<\/jats:sub>\n                      ) suggests a key role in regulating cerebrospinal fluid (CSF) K\n                      <jats:sup>+<\/jats:sup>\n                      concentration ([K\n                      <jats:sup>+<\/jats:sup>\n                      ]\n                      <jats:sub>CSF<\/jats:sub>\n                      ). We tested this hypothesis by exploring the effect of Kir7.1 inactivation or modification of its K\n                      <jats:sup>+<\/jats:sup>\n                      \u2010dependence in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We generate conditional Kir7.1 knockout (cKO) and knockin mice carrying the M125R mutation altering Kir7.1\u2009K\n                      <jats:sup>+<\/jats:sup>\n                      \u2010dependence. We study the electrical properties of CPE cells in\u00a0vitro as well as in\u00a0vivo CSF secretion and [K\n                      <jats:sup>+<\/jats:sup>\n                      ]\n                      <jats:sub>CSF<\/jats:sub>\n                      . CPE NKCC1 activity, expression and phosphorylation status were also evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Kir7.1 identified as the primary [K\n                      <jats:sup>+<\/jats:sup>\n                      ]\n                      <jats:sub>o<\/jats:sub>\n                      \u2010independent conductance in CPE cells, critically contributes to their membrane potential. CPE cells from Kir7.1\u2010M125R mice exhibited a K\n                      <jats:sup>+<\/jats:sup>\n                      conductance with direct dependence on [K\n                      <jats:sup>+<\/jats:sup>\n                      ]\n                      <jats:sub>o<\/jats:sub>\n                      . While CSF secretion rates were unaltered in both cKO Kir7.1 and M125R animals, [K\n                      <jats:sup>+<\/jats:sup>\n                      ]\n                      <jats:sub>CSF<\/jats:sub>\n                      was significantly decreased in cKO mice and increased in M125R mutants. Unexpectedly, NKCC1 activity was strongly inhibited in Kir7.1 cKO CPE despite unaltered expression and phosphorylation levels, but remained unaffected in M125R cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Kir7.1 imparts high K\n                      <jats:sup>+<\/jats:sup>\n                      permeability and defines the membrane potential of CPE cells. Its unusual [K\n                      <jats:sup>+<\/jats:sup>\n                      ]\n                      <jats:sub>o<\/jats:sub>\n                      \u2010independent conductance underpins its important role in the regulation of [K\n                      <jats:sup>+<\/jats:sup>\n                      ]\n                      <jats:sub>CSF<\/jats:sub>\n                      . Moreover, Kir7.1 appears crucial for NKCC1 function, likely these two proteins forming part of an apical complex with the Na\n                      <jats:sup>+<\/jats:sup>\n                      \u2010K\n                      <jats:sup>+<\/jats:sup>\n                      \u2010ATPase. Given the continuity of CSF with brain interstitial space, Kir7.1\u2010mediated control of [K\n                      <jats:sup>+<\/jats:sup>\n                      ]\n                      <jats:sub>CSF<\/jats:sub>\n                      might influence neuronal excitability.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.70129","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T17:35:07Z","timestamp":1762796107000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Role of the Choroid Plexus Kir7.1 Channel in the Regulation of Mouse Cerebrospinal Fluid K\n                    <sup>+<\/sup>\n                    Concentration"],"prefix":"10.1111","volume":"241","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4958-2456","authenticated-orcid":false,"given":"Juan Carlos","family":"Henao","sequence":"first","affiliation":[{"name":"Centro de Estudios Cient\u00edficos (CECs)  Valdivia Chile"},{"name":"Facultad de Medicina Universidad San Sebasti\u00e1n  Valdivia Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9563-2729","authenticated-orcid":false,"given":"Johanna","family":"Burgos","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cient\u00edficos (CECs)  Valdivia Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6887-5237","authenticated-orcid":false,"given":"Erwin","family":"Vera","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cient\u00edficos (CECs)  Valdivia Chile"},{"name":"Facultad de Medicina Universidad San Sebasti\u00e1n  Valdivia Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3985-384X","authenticated-orcid":false,"given":"Iv\u00e1n","family":"Ruminot","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cient\u00edficos (CECs)  Valdivia Chile"},{"name":"Facultad de Ciencias de la Rehabilitaci\u00f3n y Calidad de Vida Universidad San Sebasti\u00e1n  Valdivia Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0394-0498","authenticated-orcid":false,"given":"L. 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